{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:00:57Z","timestamp":1781632857173,"version":"3.54.5"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine","award":["2024216"],"award-info":[{"award-number":["2024216"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hereditas"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study evaluated the regenerative potential of nano-silver small intestine submucosa (NSSIS) scaffolds with a 4-D porous structure for repairing osteochondral defects in rabbit knee joints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NSSIS scaffolds were prepared using nanosilver, fresh pig-derived small intestinal submucosa, and chondrocytes. Biocompatibility was assessed by methyl thiazolyl tetrazolium (MTT) assays measuring bone marrow stromal cell (BMSC) proliferation at 24, 48, and 72\u00a0h. A rabbit model of intercondylar groove cartilage defects was established and randomized into three groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912 each): NSSIS, NSSIS\u2009+\u2009BMSCs, and a control group. Scaffold morphology and cell growth were evaluated in vitro using H&amp;E staining after 24\u00a0h. Following implantation, cartilage repair was assessed at 24, 48, and 72\u00a0h using ICRS macroscopic scoring and histological staining (H&amp;E, Safranin O-fast green, toluidine blue). After 12 weeks, ELISA measured growth factor expression (PDGF, VEGF, TGF-\u03b2, IGF-1, FGF, EGF), and qRT-PCR and Western blotting assessed autophagy-related gene and protein expression (AMPK, ULK1, mTOR, and Beclin-1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both NSSIS groups demonstrated significantly greater BMSC ingrowth compared with controls, with the NSSIS\u2009+\u2009BMSCs group exhibiting the most robust repair. This group showed significantly elevated growth factor expression at 12 weeks (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), downregulation of AMPK, ULK1, and Beclin-1, and upregulation of mTOR (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Histological analysis revealed enhanced chondrocyte formation, thicker cartilage layers, increased chondroblast proliferation, and abundant extracellular matrix deposition in the NSSIS\u2009+\u2009BMSCs group, whereas the NSSIS-only group showed less cellular and collagen development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NSSIS scaffolds demonstrate good biocompatibility and promote BMSC ingrowth, chondrocyte development, and osteochondral repair. The addition of BMSCs further enhances these effects by facilitating in situ chondrogenic differentiation, stimulating BMSC and chondrocyte migration, and initiating tissue regeneration. These findings highlight the potential of NSSIS, particularly when combined with BMSCs, as a promising biomaterial for cartilage and subchondral bone repair, with potential clinical applications in regenerative medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41065-026-00635-4","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T03:35:45Z","timestamp":1768793745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of nano-silver small intestine submucosa repair of osteochondral defect in rabbit model by the AMPK-mTOR-ULK1 pathway"],"prefix":"10.1186","volume":"163","author":[{"given":"Heng-Shu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"issue":"1","key":"635_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02684-z","volume":"16","author":"F Migliorini","year":"2021","unstructured":"Migliorini F, Eschweiler J, Schenker H, Baroncini A, Tingart M, Maffulli N. Surgical management of focal chondral defects of the knee: a Bayesian network meta-analysis. J Orthop Surg Res. 2021;16(1):543. https:\/\/doi.org\/10.1186\/s13018-021-02684-z.","journal-title":"J Orthop Surg Res"},{"issue":"10","key":"635_CR2","doi-asserted-by":"publisher","first-page":"2853","DOI":"10.1177\/03635465211029642","volume":"50","author":"F Migliorini","year":"2022","unstructured":"Migliorini F, Maffulli N, Schenker H, Eschweiler J, Driessen A, Knobe M, et al. Surgical management of focal chondral defects of the talus: a bayesian network meta-analysis. Am J Sports Med. 2022;50(10):2853\u20139. https:\/\/doi.org\/10.1177\/03635465211029642.","journal-title":"Am J Sports Med"},{"issue":"6","key":"635_CR3","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1093\/jbmr\/zjae069","volume":"39","author":"D Trompet","year":"2024","unstructured":"Trompet D, Melis S, Chagin AS, Maes C. Skeletal stem and progenitor cells in bone development and repair. J Bone Miner Res. 2024;39(6):633\u201354. https:\/\/doi.org\/10.1093\/jbmr\/zjae069.","journal-title":"J Bone Miner Res"},{"issue":"4 Suppl 1","key":"635_CR4","first-page":"41","volume":"30","author":"R Papalia","year":"2016","unstructured":"Papalia R, Diaz Balzani L, Torre G, Tirindelli MC, Nobile C, Maffulli N, et al. Intraoperative application platelet rich fibrin, postoperative injections of PRP or microfracture only for osteochondral lesions of the knee: a five-year retrospective evaluation. J Biol Regul Homeost Agents. 2016;30(4 Suppl 1):41\u20139.","journal-title":"J Biol Regul Homeost Agents"},{"issue":"11","key":"635_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/life12111738","volume":"12","author":"F Migliorini","year":"2022","unstructured":"Migliorini F, Maffulli N, Bell A, Hildebrand F, Weber CD, Lichte P. Autologous matrix-induced chondrogenesis (AMIC) for osteochondral defects of the talus: a systematic review. Life Basel. 2022;12(11):1738. https:\/\/doi.org\/10.3390\/life12111738.","journal-title":"Life Basel"},{"issue":"1","key":"635_CR6","doi-asserted-by":"publisher","first-page":"16244","DOI":"10.1038\/s41598-022-20641-6","volume":"12","author":"F Migliorini","year":"2022","unstructured":"Migliorini F, Schenker H, Maffulli N, Eschweiler J, Lichte P, Hildebrand F, Weber CD. Autologous matrix induced chondrogenesis (AMIC) as revision procedure for failed AMIC in recurrent symptomatic osteochondral defects of the talus. Sci Rep. 2022;12(1):16244. https:\/\/doi.org\/10.1038\/s41598-022-20641-6.","journal-title":"Sci Rep"},{"issue":"3","key":"635_CR7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.2106\/JBJS.20.01800","volume":"104","author":"CJ Bush","year":"2022","unstructured":"Bush CJ, Grant JA, Krych AJ, Bedi A. The role of mesenchymal stromal cells in the management of knee chondral defects. J Bone Joint Surg Am. 2022;104(3):284\u201392. https:\/\/doi.org\/10.2106\/JBJS.20.01800.","journal-title":"J Bone Joint Surg Am"},{"issue":"3","key":"635_CR8","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3390\/bioengineering11030211","volume":"11","author":"MJ Lammi","year":"2024","unstructured":"Lammi MJ, Qu C. Regulation of oxygen tension as a strategy to control chondrocytic phenotype for cartilage tissue engineering and regeneration. Bioeng (Basel). 2024;11(3):211\u201340. https:\/\/doi.org\/10.3390\/bioengineering11030211.","journal-title":"Bioeng (Basel)"},{"issue":"9","key":"635_CR9","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1007\/s00167-018-5278-7","volume":"27","author":"C Becher","year":"2019","unstructured":"Becher C, Malahias MA, Ali MM, Maffulli N, Thermann H. Arthroscopic microfracture vs. arthroscopic autologous matrix-induced chondrogenesis for the treatment of articular cartilage defects of the talus. Knee Surg Sports Traumatol Arthrosc. 2019;27(9):2731\u20136. https:\/\/doi.org\/10.1007\/s00167-018-5278-7.","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"635_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2024.1477724","volume":"12","author":"Y Do\u011fan","year":"2024","unstructured":"Do\u011fan Y, \u00d6zi\u00e7 C, Erta\u015f E, Baran A, Rosic G, Selakovic D, et al. Activated carbon-coated iron oxide magnetic nanocomposite (IONPs@CtAC) loaded with morin hydrate for drug-delivery applications. Front Chem. 2024;12:1477724. https:\/\/doi.org\/10.3389\/fchem.2024.1477724.","journal-title":"Front Chem"},{"key":"635_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1482130","volume":"15","author":"C \u00d6zi\u00e7","year":"2024","unstructured":"\u00d6zi\u00e7 C, Erta\u015f E, Baran MF, Baran A, Ahmadian E, Eftekhari A, et al. Synthesis and characterization of activated carbon-supported magnetic nanocomposite (MNPs-OLAC) obtained from okra leaves as a nanocarrier for targeted delivery of morin hydrate. Front Pharmacol. 2024;15:1482130. https:\/\/doi.org\/10.3389\/fphar.2024.1482130.","journal-title":"Front Pharmacol"},{"issue":"1","key":"635_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56872-0","volume":"16","author":"X Bi","year":"2025","unstructured":"Bi X, Mao Z, Li L, Zhang Y, Yang L, Hou S, et al. Janus decellularized membrane with anisotropic cell guidance and anti-adhesion silk-based coatings for spinal dural repair. Nat Commun. 2025;16(1):1674. https:\/\/doi.org\/10.1038\/s41467-025-56872-0.","journal-title":"Nat Commun"},{"issue":"6","key":"635_CR13","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/s41565-024-01624-2","volume":"19","author":"Y Wang","year":"2024","unstructured":"Wang Y, Li S, Hu M, Yang Y, McCabe E, Zhang L, et al. Universal STING mimic boosts antitumour immunity via preferential activation of tumour control signalling pathways. Nat Nanotechnol. 2024;19(6):856\u201366. https:\/\/doi.org\/10.1038\/s41565-024-01624-2.","journal-title":"Nat Nanotechnol"},{"issue":"8","key":"635_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12351","volume":"12","author":"C Chen","year":"2023","unstructured":"Chen C, Cai N, Niu Q, Tian Y, Hu Y, Yan X. Quantitative assessment of lipophilic membrane dye-based labelling of extracellular vesicles by nano-flow cytometry. J Extracell Vesicles. 2023;12(8):e12351. https:\/\/doi.org\/10.1002\/jev2.12351.","journal-title":"J Extracell Vesicles"},{"key":"635_CR15","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.actbio.2024.05.002","volume":"181","author":"M Danalache","year":"2024","unstructured":"Danalache M, Umrath F, Riester R, Schwitalle M, Guilak F, Hofmann UK. Proteolysis of the pericellular matrix: pinpointing the role and involvement of matrix metalloproteinases in early osteoarthritic remodeling. Acta Biomater. 2024;181:297\u2013307. https:\/\/doi.org\/10.1016\/j.actbio.2024.05.002.","journal-title":"Acta Biomater"},{"issue":"Special Issue","key":"635_CR16","doi-asserted-by":"publisher","first-page":"97","DOI":"10.62476\/abes9s97","volume":"9","author":"S Peyman","year":"2024","unstructured":"Peyman S, Sara A, Soroush M, Saeid G, Samad K. Nanobiomaterials\/bioinks based scaffolds in 3D bioprinting for tissue engineering and artificial human organs. Adv Biol Earth Sci. 2024;9(Special Issue):97\u2013104. https:\/\/doi.org\/10.62476\/abes9s97.","journal-title":"Adv Biol Earth Sci"},{"issue":"Special Issue","key":"635_CR17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.62476\/abes9s11","volume":"9","author":"G Rosic","year":"2024","unstructured":"Rosic G, Selakovic D, Omarova S. Cancer signaling, cell\/gene therapy, diagnosis and role of nanobiomaterials. Adv Biol Earth Sci. 2024;9(Special Issue):11\u201334. https:\/\/doi.org\/10.62476\/abes9s11.","journal-title":"Adv Biol Earth Sci"},{"issue":"3","key":"635_CR18","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1177\/0363546511431238","volume":"40","author":"O Mei-Dan","year":"2012","unstructured":"Mei-Dan O, Carmont MR, Laver L, Mann G, Maffulli N, Nyska M. Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med. 2012;40(3):534\u201341. https:\/\/doi.org\/10.1177\/0363546511431238.","journal-title":"Am J Sports Med"},{"issue":"1","key":"635_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s13770-022-00487-9","volume":"20","author":"S Duchi","year":"2023","unstructured":"Duchi S, Francis SL, Onofrillo C, O\u2019Connell CD, Choong P, Di Bella C. Towards clinical translation of in situ cartilage engineering strategies: optimizing the critical facets of a cell-laden hydrogel therapy. Tissue Eng Regen Med. 2023;20(1):25\u201347. https:\/\/doi.org\/10.1007\/s13770-022-00487-9.","journal-title":"Tissue Eng Regen Med"},{"issue":"2","key":"635_CR20","doi-asserted-by":"publisher","first-page":"262","DOI":"10.62476\/abes.102262","volume":"10","author":"A Narmina","year":"2025","unstructured":"Narmina A, Ayse B, Mahmut Y, Dashgin G, Safura B, Zubeyit G, et al. Synthesis of plant-derived selenium nanoparticles from lankaran-astara tea (camellia sinensis L.) plant and evaluation of their activities on different enzymes. Adv Biol Earth Sci. 2025;10(2):262\u20139. https:\/\/doi.org\/10.62476\/abes.102262.","journal-title":"Adv Biol Earth Sci"},{"issue":"3","key":"635_CR21","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1053\/j.jfas.2021.06.011","volume":"61","author":"A Saxena","year":"2022","unstructured":"Saxena A, Maffulli N, Jin A, Isa E, Jaswal J, Allen R. Outcomes of talar osteochondral and transchondral lesions using an algorithmic approach based on size, location, and subchondral plate integrity: a 10-year study on 204 lesions. J Foot Ankle Surg. 2022;61(3):442\u20137. https:\/\/doi.org\/10.1053\/j.jfas.2021.06.011.","journal-title":"J Foot Ankle Surg"},{"issue":"2","key":"635_CR22","doi-asserted-by":"publisher","first-page":"208","DOI":"10.62476\/abes.102208","volume":"10","author":"M Evcil","year":"2025","unstructured":"Evcil M, Kurt B, Baran A, Mouhoub A, Karakaplan M. Development, characterization and application of chitosan-based formulation incorporating crataegus orientalis extract for food conservation. Adv Biol Earth Sci. 2025;10(2):208\u201325. https:\/\/doi.org\/10.62476\/abes.102208.","journal-title":"Adv Biol Earth Sci"},{"issue":"1","key":"635_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s40634-015-0037-x","volume":"3","author":"CJ Moran","year":"2016","unstructured":"Moran CJ, Ramesh A, Brama PA, O\u2019Byrne JM, O\u2019Brien FJ, Levingstone TJ. The benefits and limitations of animal models for translational research in cartilage repair. J Exp Orthop. 2016;3(1):1. https:\/\/doi.org\/10.1186\/s40634-015-0037-x.","journal-title":"J Exp Orthop"},{"issue":"5","key":"635_CR24","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1177\/03635465241234534","volume":"52","author":"M Husen","year":"2024","unstructured":"Husen M, Wang AS, Levy BA, Saris DBF, Stuart MJ, Krych AJ. Influence of concomitant meniscal allograft transplantation on midterm outcomes after osteochondral allograft transplantation: a comparative matched-pair analysis. Am J Sports Med. 2024;52(5):1238\u201349. https:\/\/doi.org\/10.1177\/03635465241234534.","journal-title":"Am J Sports Med"},{"issue":"12","key":"635_CR25","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1177\/03635465211037349","volume":"50","author":"F Migliorini","year":"2022","unstructured":"Migliorini F, Maffulli N, Baroncini A, Eschweiler J, Knobe M, Tingart M, et al. Allograft versus autograft osteochondral transplant for chondral defects of the talus: systematic review and meta-analysis. Am J Sports Med. 2022;50(12):3447\u201355. https:\/\/doi.org\/10.1177\/03635465211037349.","journal-title":"Am J Sports Med"},{"issue":"1","key":"635_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.fcl.2012.12.002","volume":"18","author":"GA McCollum","year":"2013","unstructured":"McCollum GA, Calder JD, Longo UG, Loppini M, Romeo G, van Dijk CN, et al. Talus osteochondral bruises and defects: diagnosis and differentiation. Foot Ankle Clin. 2013;18(1):35\u201347. https:\/\/doi.org\/10.1016\/j.fcl.2012.12.002.","journal-title":"Foot Ankle Clin"},{"issue":"2","key":"635_CR27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1089\/ten.TEC.2021.0208","volume":"28","author":"JPC SantAnna","year":"2022","unstructured":"SantAnna JPC, Faria RR, Assad IP, Pinheiro CCG, Aiello VD, Albuquerque-Neto C, Bortolussi R, Cestari IA, Maizato MJS, Hernandez AJ, Bueno DF, Fernandes TL. Tissue engineering and cell therapy for cartilage repair: preclinical evaluation methods. Tissue Eng Part C Methods. 2022;28(2):73\u201382. https:\/\/doi.org\/10.1089\/ten.TEC.2021.0208.","journal-title":"Tissue Eng Part C Methods"},{"issue":"5","key":"635_CR28","first-page":"715","volume":"22","author":"YH Liu","year":"2024","unstructured":"Liu YH, Liu XG. Autologous costal cartilage transplantation to repair severe deafness. Chin J Otol. 2024;22(5):715\u20137.","journal-title":"Chin J Otol"},{"issue":"6","key":"635_CR29","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1002\/lio2.963","volume":"7","author":"P Dontu","year":"2022","unstructured":"Dontu P, Shaigany K, Eisenman DJ. Anatomic and audiometric outcomes of porcine intestinal submucosa for tympanic membrane repair. Laryngoscope Investig Otolaryngol. 2022;7(6):2069\u201375. https:\/\/doi.org\/10.1002\/lio2.963.","journal-title":"Laryngoscope Investig Otolaryngol"},{"issue":"5","key":"635_CR30","doi-asserted-by":"publisher","first-page":"887","DOI":"10.19723\/j.issn.1671-167X.2019.05.016","volume":"51","author":"BW Li","year":"2019","unstructured":"Li BW, Wu WY, Tang L, Zhang Y, Liu YH. [Barrier effect of improved porcine small intestinal submucosa absorbable membrane on early healing of mandibular defects in rabbits]. Beijing Da Xue Xue Bao Yi Xue Ban. 2019;51(5):887\u201392. https:\/\/doi.org\/10.19723\/j.issn.1671-167X.2019.05.016.","journal-title":"Beijing Da Xue Xue Bao Yi Xue Ban"},{"issue":"3","key":"635_CR31","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1039\/d4nr03322a","volume":"17","author":"S Awasthi","year":"2025","unstructured":"Awasthi S, Pandey SK, Shwetha HJ, Nehal, Selvaraj S. Tough, durable and strongly bonded self-healing cartilage-mimicking noncovalently assembled hydrogel nanostructures: the interplay between experiment and theory. Nanoscale. 2025;17(3):1616\u201343. https:\/\/doi.org\/10.1039\/d4nr03322a.","journal-title":"Nanoscale"},{"issue":"1","key":"635_CR32","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3969\/j.issn.1674-8115.2024.01.002","volume":"44","author":"ZY Zhu","year":"2024","unstructured":"Zhu ZY, Lv CQ, Liu XL, Chen YL, Zou DR, Lu JY. Observation on A-PRF promoting regeneration of osteochondral defects in rabbit knee joints. J Shanghai Jiaotong Uni. 2024;44(1):13\u201322. https:\/\/doi.org\/10.3969\/j.issn.1674-8115.2024.01.002.","journal-title":"J Shanghai Jiaotong Uni"},{"issue":"3","key":"635_CR33","doi-asserted-by":"publisher","first-page":"232","DOI":"10.2106\/JBJS.23.00294","volume":"106","author":"M Wang","year":"2024","unstructured":"Wang M, Li Y, Lin S, Ong MTY, Yung PSH, Li G. In vivo effect of single intra-articular injection of tranexamic acid on articular cartilage and meniscus: study in a rat model. J Bone Joint Surg Am. 2024;106(3):232\u201340. https:\/\/doi.org\/10.2106\/JBJS.23.00294.","journal-title":"J Bone Joint Surg Am"},{"key":"635_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.110119","volume":"248","author":"DF Lara-Santofimio","year":"2024","unstructured":"Lara-Santofimio DF, Bonilla-Escobar FJ. Comment on: \u201cTherapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.\u201d Exp Eye Res. 2024;248:110119. https:\/\/doi.org\/10.1016\/j.exer.2024.110119.","journal-title":"Exp Eye Res"},{"issue":"10","key":"635_CR35","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.3390\/ijms25105242","volume":"25","author":"JY Kim","year":"2024","unstructured":"Kim JY, Lee SY, Cha SG, Park JM, Song DH, Lee SH, et al. Combinatory nanovesicle with siRNA-loaded extracellular vesicle and\u2002IGF-1\u2002for osteoarthritis treatments. Int J Mol Sci. 2024;25(10):5242\u201360. https:\/\/doi.org\/10.3390\/ijms25105242.","journal-title":"Int J Mol Sci"},{"key":"635_CR36","doi-asserted-by":"publisher","DOI":"10.1177\/20417314241268189","volume":"15","author":"W Zhu","year":"2024","unstructured":"Zhu W, Shi J, Weng B, Zhou Z, Mao X, Pan S, et al. EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration. J Tissue Eng. 2024;15:20417314241268189. https:\/\/doi.org\/10.1177\/20417314241268189.","journal-title":"J Tissue Eng"},{"key":"635_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2024.102380","volume":"88","author":"M Mamachan","year":"2024","unstructured":"Mamachan M, Sharun K, Banu SA, Muthu S, Pawde AM, Abualigah L, et al. Mesenchymal stem cells for cartilage regeneration: insights into molecular mechanism and therapeutic strategies. Tissue Cell. 2024;88:102380. https:\/\/doi.org\/10.1016\/j.tice.2024.102380.","journal-title":"Tissue Cell"},{"issue":"4","key":"635_CR38","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1021\/acsbiomaterials.3c01629","volume":"10","author":"C Zhang","year":"2024","unstructured":"Zhang C, Cai X, Li M, Peng J, Mei J, Wang F, Zhang R, Zhou Y, Fang S, Xia D, Zhao J. Preclinical evaluation of bioactive small intestinal Submucosa-PMMA bone cement for vertebral augmentation. ACS Biomater Sci Eng. 2024;10(4):2398\u2013413. https:\/\/doi.org\/10.1021\/acsbiomaterials.3c01629.","journal-title":"ACS Biomater Sci Eng"},{"key":"635_CR39","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jconrel.2022.05.027","volume":"347","author":"I Kimiz-Gebologlu","year":"2022","unstructured":"Kimiz-Gebologlu I, Oncel SS. Exosomes: large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J Control Release. 2022;347:533\u201343. https:\/\/doi.org\/10.1016\/j.jconrel.2022.05.027.","journal-title":"J Control Release"},{"issue":"5","key":"635_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2023.103961","volume":"44","author":"OE Speed","year":"2023","unstructured":"Speed OE, Bareiss A, Patel VA, Mangan A, Dornhoffer J, Saadi RA. Otologic use of porcine small intestinal submucosal graft (biodesign): a MAUDE database review. Am J Otolaryngol. 2023;44(5):103961. https:\/\/doi.org\/10.1016\/j.amjoto.2023.103961.","journal-title":"Am J Otolaryngol"},{"issue":"6","key":"635_CR41","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1177\/03635465231164952","volume":"51","author":"MJ Matava","year":"2023","unstructured":"Matava MJ, Gibian JT, Hutchinson LE, Miller PE, Milewski MD, Pennock AT, et al. Factors associated with meniscal and articular cartilage injury in the PLUTO cohort. Am J Sports Med. 2023;51(6):1497\u2013505. https:\/\/doi.org\/10.1177\/03635465231164952.","journal-title":"Am J Sports Med"},{"issue":"1","key":"635_CR42","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.spinee.2023.07.018","volume":"24","author":"JD Zehr","year":"2024","unstructured":"Zehr JD, Quadrilatero J, Callaghan JP. Initiation and accumulation of loading induced changes to native collagen content and microstructural damage in the cartilaginous endplate. Spine J. 2024;24(1):161\u201371. https:\/\/doi.org\/10.1016\/j.spinee.2023.07.018.","journal-title":"Spine J"},{"issue":"8","key":"635_CR43","first-page":"1516","volume":"39","author":"Y Tao","year":"2022","unstructured":"Tao Y, Li GB, Zhang HY, Cao K, Wang ZJ, Han JG. Healing mechanism of anal fistula treated by nano-silver and porcine small intestinal submucosa. Chin J Exp Surg. 2022;39(8):1516\u201322.","journal-title":"Chin J Exp Surg"},{"key":"635_CR44","doi-asserted-by":"publisher","unstructured":"Lai C, Liao B, Peng S, Fang P, Bao N, Zhang L. Synovial fibroblast-miR-214-3p-derived exosomes inhibit inflammation and degeneration of cartilage tissues ofosteoarthritis rats. Mol Cell Biochem. 2023;478(3):637\u201349. https:\/\/doi.org\/10.1007\/s11010-022-04535-9.","DOI":"10.1007\/s11010-022-04535-9"}],"container-title":["Hereditas"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41065-026-00635-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41065-026-00635-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41065-026-00635-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:48:35Z","timestamp":1781632115000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41065-026-00635-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["635"],"URL":"https:\/\/doi.org\/10.1186\/s41065-026-00635-4","relation":{},"ISSN":["1601-5223"],"issn-type":[{"value":"1601-5223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,19]]},"assertion":[{"value":"4 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted with approval from the Ethics Committee of the Second Hospital of Hebei Medical University Traditional Chinese Medicine Hospital of Hebei Province. All applicable international, national, and\/or institutional guidelines for the care and use of animals were followed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare that they have no conflict of interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"25"}}